HPA axis dysfunction

There are two primary ways in which the HPA axis (read an overview of the axis and what it does here) can malfunction: its activity can increase, or its activity can decrease. I discuss increased and decreased adrenal and pituitary function below.

Why all this talk on the HPA Axis? Because, as we know, hormone function is crucial for happiness and health. For more, check out my bestseller or Dr. Sara Gottfried’s book.

HPA Axis: Increased adrenal activity

The HPA axis jumps into action when stressed or stimulated. This is a good thing when the body is faced with short-term stressors.

In this event, adrenal activity increases. The adrenal glands keep people alive in the face of a threat: they rally the body’s resources into “fight or flight” mode using cortisol and adrenaline.

Healthy adrenals instantaneously increase heart rate and blood pressure, release energy stores for immediate use, shut down digestion and other secondary functions, and sharpen the senses. This is awesome.

But since they are programmed to respond to every kind of stress — physical, emotional, perceived, psychological, environmental, infectious, or any combination of these — a person under chronic stress can get into a fair bit of trouble.

Chronic stress can knock the whole HPA axis off kilter. Other conditions that can do the same are: Depression, Anorexia, OCD, Anxiety disorders, Excessive exercise, Alcoholism, Withdrawal, Diabetes, Obesity, Metabolic Syndrome, and hypothyroidism.

The result is over-activity, which can result in jittery feelings and insomnia. Eventually, this can turn into a chronic “tired and wired” feeling, as well as long-term health problems such as adrenal fatigue, hypothyroidism, inflammation, diabetes, autoimmune disease, and mental health problems.

Why an over-active adrenal gland is unpleasant

1) Cortisol is immunosupressive. Cortisol impairs cytokine production and function, induces the loss of tissues important to immune cell production, and may in fact play a causative role in the development of autoimmune disease.

Being immunosupressive also means that cortisol inhibits inflammation. Usually we’d think of this as a good thing, but when it goes on for too long, important inflammatory reactions, including the immune reactions I just mentioned, fail to function when they are needed.

2) Cortisol decreases hormonal output. Cortisol signals to the hypothalamus to down-regulate, which makes growth hormone, thyroid releasing hormone, and gonadotropin releasing hormone get released at much lower rates by the hypothalamus. Yikes!

Without GH you don’t grow; without TSH your thyroid doesn’t work properly; and without GnRH your pituitary fails to initiate reproductive activity. GnRH is a factor in just about every single endocrine disorder.

To top it off, these hormones act as cortisol antagonists. They can blunt the effect of cortisol. This makes their absence is even more dangerous. Without them, cortisol can increase without ever being checked.

3) Cortisol increases insulin levels. This can lead to both hyperinsulinemia and fat deposition. Visceral fat has buckets full of cortisol receptors in it, which makes it very easy for cortisol and insulin to shuttle triglycerides into fat cells.

It can also be a causative factor in PCOS, since high insulin levels cause testosterone levels to rise. It’s not common for people to talk about this as a cause of PCOS – but it is very real. You can read more about my thoughts on PCOS, and how to overcome it, here.

4) Increases in cortisol-induced abdominal fat are associated with an increase in both total oxidative stress and in the number of inflammatory cytokines.

5) Cortisol can destroy healthy muscle and bone tissue.

HPA Axis: Decreased adrenal activity

Decreased HPA axis and adrenal activity may be even worse than increased (unfortunately they often occur together, alternating between one or the other).

The HPA axis decreases its activity levels sometimes when told to do so, as is the case when leptin levels are low. Low leptin signals to the hypothalamus that the body has not been properly fed, so the hypothalamus tells the pituitary, adrenal, and thyroid glands to slow down and wait for the body to get more energy from food. Sometimes the best thing a woman can do for her body is simply feed it.

The HPA axis also decreases its activity when it becomes exhausted by being in a high-stress, hyper-active mode for too long a time period. Some people call this “adrenal fatigue” – I choose not to.

3) High-stress sensitivity, chronic fatigue and chronic pain. These three occur so frequently and in such concert with low cortisol states that they are referred to as the “low cortisol triad” by some authors. I know. Catchy.

The Adrenals and DHEA-S

DHEA-S is produced by the adrenal cortex. It is an androgen, and it is considered one of the dominant precursor hormones. This makes it critical for endocrine and reproductive function. DHEA-S is produced in other organs, but it’s primary source is the adrenal glands.

High levels of DHEA-S are often associated with hyper-activity of the adrenal glands- so in this case both cortisol and DHEA-S are elevated in the blood. The HPA axis has started pumping, and it doesn’t know how to stop. Women with PCOS often have high levels of DHEA-S precisely for this reason. This is bad for them because it makes it much easier to create androgens such as testosterone. And without parallel increases in estrogen from the ovaries, the excess testosterone will wreak havoc.

To read more about DHEA-S and it’s relationship with PCOS, check out my post here.

Calorie restriction and exercise both also increase DHEA-S levels. DHEA-S is the primary hormone, and DHEA is the active form. When calories are consumed, more DHEA is recruited form DHEA-S. This depletes DHEA-S stories. So calorie consumption reduces DHEA-S, but calorie restriction will keep levels higher longer.

This is important to note for those of us who restrict calories and exercise frequently. If we have hormone problems, particularly issue with excess, we might want to think about how to optimize our DHEA-S production. Too much DHEA-S? Eat more. Too little? Try eating a bit less, or intermittent fasting.

Low levels of DHEA-S on the other hand are associated with adrenal fatigue and hypocortisolism. In this case, the HPA axis just can’t do much of anything anymore. This is not great news. You need DHEA-S and DHEA in order to feel energized and happy. DHEA is in fact considered the best “feel good” hormone by many endocrinologists. And it is a precursor to many hormones.

Moreover, there is a growing body of evidence that healthy levels of DHEA and DHEA-S may help stave off Alzheimer’s disease, cancer, osteoporosis, depression, heart disease and obesity. You can supplement with DHEA-S if you feel as though you desperately need it. However, perhaps the best course is to supplement in the meantime while you address the underlying issue of decreased HPA axis activity and adrenal exhaustion.

The pituitary

Because stress is a big deal and everyone wants to know about it, most of the research on the HPA axis has focused on cortisol and the adrenals. But the rest of the axis is important, too.

Increasing hypothalamic activity via the adrenals is unhealthy because cortisol and the other stress hormones interfere with the activity of sex hormones. They also, as mentioned, steal the resources necessary in order to make sex hormones. When hypothalamic activity is increased, hormone levels often fall.

When hypothalamic activity is decreased, horomone levels almost always fall.

The thyroid

While not technically a part of the “HPA axis” the thyroid gland is still intimately connected with this system. This is why it is also sometimes known as the HPAT axis.

The thyroid gland is as negatively affected by stress as the pitiutary gland. Cortisol also interferes with healthy thyroid hormone production. And TSH, the one hormone responsible for telling the thyroid gland to go ahead and do it’s job, is secreted by the pituitary gland. If pituitary function fails, so does thyroid function.

Causes of decreased HPA axis activity

Many things cause the HPA axis to falter. All of them ultimately boil down to stress of one sort or another.

1) Decreased leptin levels. Leptin is secreted by fat cells and in response to meals (the best response is to meals with carbohydrate in them). It is the primary hormone responsible for telling the hypothalamus that a woman has been sufficiently fed.

If leptin signalling is weak–ie, if our body fat levels are too low, or if we exercise too often–then the lack of leptin crossing the blood-brain barrier into the hypothalamus signals to the hypothalamus that the body is starving, and certain extraneous bodily functions such as reproduction cease.

3) Exhaustion of resources. HPA axis activity can decrease if it has become exhausted. Certain vitamins, like B vitamins, vitamin C, zinc, and magnesium, are very helpful for adrenal function. When these resources run dry, the adrenal glands can become unproductive.

In all of these cases, the hypothalamus stops telling the pituitary gland to produce sex hormones. The pituitary, in turn, stops telling the gonadal tissue to produce hormones like estrogen. The end result is overall decreased sex hormone levels.

Sex hormones are necessary for reproductive function, as well as for a variety of other important roles such as waking the body up, putting it to sleep, being in a good mood, and having a good memory. When sex hormones decrease, many things can go wrong. PCOS is one them. Acne is another. Loss of libido, too, and also, fertility. Depression. Weight gain. Miscarriage. Yikes.

So the solution?

Sleep as much as possible. Eat the appropriate amount of food. Rest often. Refuse to be stressed. I am a firm, firm believer in the power of positivity to make us healthy human beings, and the HPA axis probably plays a big role in that. Don’t let your co-workers, your boss, whatever, all that nasty crap in your life get you down. I mean– it’s a million times more complicated than that. I understand. But I really do think mitigating those stressors (especially the ones you impose on yourself!) transforms physical health. No self-hating, no anxiety about your looks, no worries about being perfect. Your cells will thank you.

If you want to read more about hormones, stress, and your health and happiness, I have a whole book on the subject that is – well, it’s the place I went to dump all the knowledge I have about all the things, and what to do about it. You can check it out, here.

*Thank you WomenToWomen for the awesome graphics!

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Adrenal fatigue is a term applied to a collection of nonspecific symptoms, such as body aches, fatigue, nervousness, sleep disturbances and digestive problems. The term often shows up in popular health books and on alternative medicine websites, but it isn’t an accepted medical diagnosis.

Hi Stephani! First off, thank you for writing this! You have been a big help in my journey to better health. My question is: I’m pretty sure my case is low cortisol from your list of symptoms (I have chronic inflammation, allergies, bowl movements are off, atypical depression), however I’m showing signs of low estrogen in comparison to my androgens. I’m thinking I have PCOS. Do you really recommend that I exercise more and restrict calories? Just wondering because in your other posts you recommend to get leptin levels sorted. Thanks again and have a great week!

This is me 110%. PCOS and pituitary hypothyroidism. Been trying to lose weight for two years without success and now trying to focus on figuring out how to lower stress levels… Difficult in college 🙂 Thank you for this article. Very informative and validating!

I have just been diagnosed with Graves Disease after massive stress mid August and although you don’t mention Hyperthyroid I imagine it fits in here too. I’m considering an autoimmune diet very seriously even if I have to take the drugs. And make time for rest, joy and other good things. Trying not to catastrophize!! (but a bit scared really)

Definitely not a catastrophe! Though you are correct – I would absolutely treat Graves as an autoimmune disorder. My condolences for your stress and diagnosis, and also congratulations on taking these important steps in your journey 🙂

Interesting article! I’m keen on knowing more about the relation between anxiety and hormones and this gave very detailed information. Personally, I’ve kept my panic attacks and anxiety away for years with ketogenic diet. Basically I’m just counting my carbs and I still consume dairy as I didn’t notice it to cause any problems. However, I’m planning to move more into paleo direction and see how my body and mind reacts.